Diabetes mellitus is a chronic debilitating disease affecting over 170 million people worldwide, 5-10% of which, about 8.5 to 17 million, are type 1 diabetic (T1D) patients. T1D patients inject insulin daily to control blood glucose (BG), however, BG fluctuations and impaired glycemic control inherent to exogenous insulin administration is associated with severe complications in the long term. Consequently, diabetes is one of the leading causes of blindness, end-stage renal failure, non-traumatic limb amputations, and cardiovascular morbidity and mortality. Quality of life for diabetic patients is evidently decreased, not only in manifestation of complications, but also in managing the disease and fear of life threatening glycemic events. Cell-based therapies such as, replacement of the insulin producing pancreatic-cells by transplanting isolated human islet cells intraportally is an approach that has shown remarkable promise in restoring normoglycemia. In turn islet allotransplants have reduced the incidence for frequent and life-threatening complications associated with metabolic instability. However, a shortage of human donor pancreases exists, limiting the number of patients that can take advantage of this therapy. Exacerbating this are intraportal islet transplant protocols that require high islet numbers as a consequence of the significant loss of islets (over half is speculated) immediately post transplant to hypoxia, inflammation, and immune-mediated loss. There is general agreement that the liver may not be the ideal environment for islets because of exposure to high concentrations of glucagon, diabetogenic immunosuppressive drugs, and toxins from the gastrointestinal tract. For these reasons, and causes not fully understood, intrahepatic islets in humans exhibit a progressive loss of function. This suggests that an alternative implantation site is critically needed to achieve long-term diabetes reversal and preserve the short supply of available cells for transplantation. In the future it is likely that additional sources of cells will be an option for patients as promising results with porcine islets have been achieved in nonhuman primates. Furthermore, several groups have derived islet progenitors or differentiated cells from pluripotent stem cells. It is reasonable to expect that these cells would encounter similar challenges that have been observed in human allogeneic islet transplants if delivered intraportally. Devices that enable alternative islet transplantation sites by addressing the basic yet vital needs of islets (e.g. oxygen, nutrition, hydration, and waste disposal) have potential to enhance the translational value of these promising therapies. A number of alternative sites have been evaluated along with immune-isolation or encapsulations technologies. These approaches have a range of limitations that include premature death of the cells, inability to measure the health of the transplanted cells and the inability to retrieve the encapsulated dead cells.
There is significant interest in the field of transplanted cells, more specifically for the Islets of Langerhans preservation and immunoisolation devices. The potential for an immunoisolation device ranges from the use of transplanted porcine islet cells, to the preservation of Induced Pluripotent Cells, both for the diabetic patient population to introduce or create a plentiful supply of functioning islet cells. In addition to the use of such a device in transplanted islets, numerous other applications for transplanted cells exist.
Therefore, there exists a need for a dynamic bio-artificial pancreas, a cell transplant device designed to be a cell oasis to protect and nourish transplanted cells. The present invention will alleviate the major problems associated with islet cell loss in the engraftment phase to long-term and promote the development of an alternative islet transplantation site.